Sequential enzymatic down-regulation and degradation of the Lyn tyrosine kinase in erythropoietin-stimulated cells.

Abstract

Abstract Erythropoietin (Epo) is a key molecule in the development of red blood cells. We have shown previously that the tyrosine kinase Lyn is involved in differentiation signals emanating from an activated Epo-receptor. We have recently identified Cbp (Csk binding protein, a negative regulator of Src) as a novel interactor with Lyn. The proline-rich region of Cbp associates with the SH3 domain of Lyn, which then phosphorylates Cbp on multiple tyrosine residues forming additional binding sites for the Lyn SH2 domain. Phosphorylated Y314 of Cbp, in turn, recruits the negative regulators Csk/Ctk, which phosphorylate Lyn and down-regulate its kinase activity. A phosphotyrosine-s..